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Metabolic activity by 18F–FDG-PET/CT is predictive of early response after nivolumab in previously treated NSCLC

European Journal of Nuclear Medicine and Molecular Imaging volume 45, pages 56–66 (2018)Cite this article

Abstract

Background

Nivolumab, an anti-programmed death-1 (PD-1) antibody, is administered in patients with previously treated non-small cell lung cancer. However, little is known about the established biomarker predicting the efficacy of nivolumab. Here, we conducted a preliminary study to investigate whether 18F–FDG-PET/CT could predict the therapeutic response of nivolumab at the early phase.

Methods

Twenty-four patients were enrolled in this study. 18F–FDG-PET/CT was carried out before and 1 month after nivolumab therapy. SUVmax, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were calculated. Immunohistochemical analysis of PD-L1 expression and tumour-infiltrating lymphocytes was conducted.

Results

Among all patients, a partial metabolic response to nivolumab was observed in 29% on SUVmax, 25% on MTV, and 33% on TLG, whereas seven (29%) patients achieved a partial response (PR) based on RECIST v1.1. The predictive probability of PR (100% vs. 29%, p = 0.021) and progressive disease (100% vs. 22.2%, p = 0.002) at 1 month after nivolumab initiation was significantly higher in 18F–FDG on PET/CT than in CT scans. Multivariate analysis confirmed that 18F–FDG uptake after administration of nivolumab was an independent prognostic factor. PD-L1 expression and nivolumab plasma concentration could not precisely predict the early therapeutic efficacy of nivolumab.

Conclusion

Metabolic response by 18F–FDG was effective in predicting efficacy and survival at 1 month after nivolumab treatment.

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Acknowledgements

We thank Ms. Yuka Matsui for her technical assistance during the manuscript submission. We deeply appreciate the help provided by Ms. Yoko Tokumitsu of the Department of Outpatient Chemotherapy Center, Hidaka Hospital, Drs. Toshitaka Maeno, Kenichiro Hara, Yasuhiko Koga, and Akira Ono of the Department of Respiratory Medicine, and Drs. Toshiki Yajima and Takayuki Kosaka of the Department of Respiratory Surgery, Gunma University Hospital, for data collection and clinical advice.

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Author notes

  1. Tetsuya Higuchi and Ichiro Naruse contributed equally to this study.

Affiliations

  1. Department of Oncology Clinical Development, Gunma University Graduate School of Medicine, Showa-machi, Maebashi, Gunma, 371-8511, Japan

    Kyoichi Kaira & Bolag Altan

  2. Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan

    Tetsuya Higuchi, Yukiko Arisaka, Azusa Tokue & Yoshihito Tsushima

  3. Department of Respiratory Medicine, Hidaka Hospital, Hidaka, Japan

    Ichiro Naruse

  4. Department of Radiology, Hidaka Hospital, Hidaka, Japan

    Satoshi Suda

  5. Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan

    Akira Mogi & Kimihiro Shimizu

  6. Oncology Center, Gunma University Hospital, Maebashi, Gunma, Japan

    Noriaki Sunaga

  7. Department of Respiratory Medicine, Gunma University Hospital, Maebashi, Gunma, Japan

    Takeshi Hisada

  8. Department of Experimental Therapeutics, National Cancer Center Hospital, Tokyo, Japan

    Shigehisa Kitano

  9. Big Data Center for Integrative Analysis, Gunma University Initiative for Advanced Research, Maebashi, Gunma, Japan

    Hideru Obinata & Takayuki Asao

  10. Division of Integrated Oncology Research, Research Program for Omics-based Medical Science, Gunma University Initiative for Advanced Research, Maebashi, Gunma, Japan

    Takehiko Yokobori

  11. Clinical Research Support Center, Shizuoka Cancer Center, Suntou-gun, Japan

    Keita Mori

  12. Department of Molecular Pharmacology and Oncology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan

    Masahiko Nishiyama

  13. Research Program for Diagnostic and Molecular Imaging, Division of Integrated Oncology Research, Gunma University Initiative for Advanced Research (GIAR), Maebashi, Gunma, Japan

    Yoshihito Tsushima

Authors
  1. Kyoichi Kaira
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  2. Tetsuya Higuchi
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  3. Ichiro Naruse
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  4. Yukiko Arisaka
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  5. Azusa Tokue
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  6. Bolag Altan
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  7. Satoshi Suda
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  8. Akira Mogi
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  9. Kimihiro Shimizu
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  10. Noriaki Sunaga
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  11. Takeshi Hisada
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  12. Shigehisa Kitano
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  13. Hideru Obinata
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  14. Takehiko Yokobori
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  15. Keita Mori
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  16. Masahiko Nishiyama
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  17. Yoshihito Tsushima
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  18. Takayuki Asao
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Corresponding author

Correspondence to Kyoichi Kaira.

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Conflict of interest

KK has received research grants and speaker honoraria from Ono Pharmaceutical Company and Bristol-Myers Company. All remaining authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Kaira, K., Higuchi, T., Naruse, I. et al. Metabolic activity by 18F–FDG-PET/CT is predictive of early response after nivolumab in previously treated NSCLC. Eur J Nucl Med Mol Imaging 45, 56–66 (2018). https://doi.org/10.1007/s00259-017-3806-1

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  • DOI: https://doi.org/10.1007/s00259-017-3806-1

Keywords

  • FDG-PET
  • Nivolumab
  • Pd-L1
  • Lung cancer
  • Early response